Micro-substances such as microvesicles in blood have previously been recognized as substance having no special function. However, various experimental data have demonstrated that microvesicles also have biological activity. For example, it was found that platelet-derived microvesicles function to stimulate certain cells through vesicular surface proteins (CD154, RANTES and/or PF-4; Thromb. Haemost. (1999) 82:794; J. Biol. Chem. (1999) 274:7545), and it was reported that physiologically active lipids (e.g., HTET or arachidonic acid) in platelet microvesicles have certain effects on certain target cells (J. Biol. Chem. (2001) 276; 19672; Cardiovasc. Res. (2001) 49(5):88). Thus, because the characteristics (e.g., size, surface antigens, determination of cell-of-origin, payload) of substances such as vesicles present in biological samples, can provide a diagnostic, prognostic or theranostic readout, there remains a need to identify biological markers that can be used to detect and treat disease. Accordingly, there has been an attempt to use RNA and other biological markers associated with vesicles as well as the characteristics of vesicles to provide a diagnosis, prognosis, or theranosis (see WO 2011/127219).
Meanwhile, cancer is a disease in which cells grow abnormally to interfere with the functions of normal cells, and typical examples thereof include lung cancer, gastric cancer (GC), breast cancer (BRC), colorectal cancer (CRC) and the like, but cancer can actually occur in any tissue. In the past, the diagnosis of cancer was based on the external change of biological tissue caused by the growth of cancer cells, but in recent years, it has been attempted to perform diagnosis and detection using trace biomolecules (glycol chain, DNA, etc.) present in blood, biological tissue or cells. However, the cancer diagnostic method that is most commonly used is a diagnostic method that uses either a tissue sample obtained through biopsy or imaging. Biopsy, however, causes great pain in the patient, is costly, and requires a long time for diagnosis of cancer. In addition, if a patient has cancer, the cancer can metastasize during biopsy, and in the case of a site from which a tissue sample cannot be obtained through biopsy, there is a disadvantage in that the diagnosis of disease is impossible before a tissue suspected of having the disease is extracted by a surgical operation. Meanwhile, in diagnosis based on imaging, cancer is diagnosed based on X-ray imaging, nuclear magnetic resonance (NMR) imaging employing an imaging agent having a disease-targeting agent attached thereto, or the like. However, this imaging-based diagnostic method has disadvantages in that an erroneous diagnosis may result from the low skill of a clinical physician or an interpreting physician and in that the method greatly depends on the precision of an imaging device. Furthermore, the imaging-based diagnostic method has a disadvantage in that it is difficult to detect disease in an early stage, because even the most precise device cannot detect a tumor having a size of several mm or less. In addition, the imaging-based diagnostic method has disadvantages in that, because a patient or a person suspected of having disease is exposed to high-energy electromagnetic waves for imaging, which can cause a genetic mutation, the method can cause another disease, and in that the number of diagnoses by imaging is limited.
In other words, biopsy for cancer diagnosis is time-consuming, costly, inconvenient, and causes pain. For this reason, there is a need for a method capable of significantly reducing the number of unnecessary biopsy procedures, as well as a method capable of diagnosing cancer at an early stage.
Under such circumstances, the present inventors found that a disease can be diagnosed and predicted by observing the characteristics of a micro-substance present in a body fluid discharged from a patient. The content of this finding was filed for a patent on Jul. 12, 2013 (Korean Patent Application No. 10-2013-0082060). The present inventors named the unidentified nano-sized particle a “luterial”.
However, a technology of efficiently isolating and culturing the micro-substance luterial so as to be capable of being clinically applied has not been known.
Accordingly, the present inventors have developed a method capable of effectively isolating the unidentified nano-sized particle luterial present in a body fluid discharged from a patient or a normal person and have characterized luterial isolated by this method, thereby completing the present invention.